Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.     

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

Enhancement of adenovirus-mediated gene transfer to human bone marrow cells

Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on the multiplicity of infection (MOI), time of incubation, the volume in which the co-incubation occurs and the presence or absence of growth factors. Studies revealed that a brief co-incubation (1-8 hours), resulted in low levels of transgene expression, suggesting that adenovirus infection of CD34+ cells occurs slowly, and optimal transduction requires a 24 hour exposure to adenovirus. Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction efficiency but inhibited hematopoietic function. However, treatment at a MOI of 50-100 resulted in efficient transduction (10.7-15.7% positive) without detectable toxicity. Secondary proof of adenovirus transgene expression was demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta-gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has no significant effect on hematopoietic function. Adenovirus-mediated transduction of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with improved gene delivery and maintenance of hematopoietic function. In summary, adenovirus vectors can be used to transiently transduce stem cells, and conditions have been defined to maximize expression and limit inhibitory effects on CD34+ cells. These data support continued investigation of this vector for local cytokine delivery and purging of stem cell products.     

Effect of ergotamine and ergonovine on plasma concentrations of thyroid hormones and cortisol in cattle

Plasma samples from two experiments were processed to determine whether ergot alkaloids associated with endophyte-infected tall fescue altered peripheral thyroxine (T4), triiodothyronine (T3), or cortisol concentrations in cattle. In Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline (SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly intervals, and they received all treatments during the study. Blood was sampled every 15 min for 5 h, and treatments were given after h 1. Mean ambient temperature was 34 degrees C. Treatment x time affected plasma concentrations of T3 (P < .05) and of cortisol (P < .001) but not that of T4 (P > .2). Plasma T3 concentrations were not affected by SAL, whereas concentrations increased (P < .01) after either EM or ET treatment. Plasma cortisol concentrations were not altered by SAL or EM, but they were increased (P < .001) by ET treatment. In Exp. 2, six Holstein cows (499 kg) nursing calves received a bolus i.v. injection of SAL, EM (9.5 mg), or ET (9.5 mg) per estrous cycle, and all treatments were given over three cycles. Blood was sampled every 20 min for 5 h; treatments were given after h 1. Mean ambient temperature was 26 degrees C. Treatment x time affected T3 (P = .08) and cortisol (P < .001) and tended to influence (P = .16) T4 concentrations. Plasma T3, T4, and cortisol concentrations were not influenced by SAL treatment. Plasma T3 was higher (P < or = .01) after EM or ET treatment compared with pretreatment concentrations. Concentrations of T4 during the 4 h after EM and ET were increased (P < .001) compared with pretreatment. Plasma cortisol concentrations were not altered by EM but were increased (P < .001) by ET. Ergot alkaloids implicated as contributing agents to fescue toxicosis alter plasma concentrations of hormones important to metabolic and thermoregulatory functions in cattle.     

Isolation of single yeast cells by optical trapping

Individual yeast cells can be successfully isolated and recultured on plates with a new isolation method making use of optical trapping with infrared laser light. The cells can be selected on morphological criteria by high resolution microscopy. The isolation device is constructed from two coverslips separated by spacers, in which selected cells are transferred to a plastic capillary, using the optical trap. To test the procedure, selection experiments were done with a mixture of two Saccharomyces cerevisiae strains, distinguishable both in fluorescence microscopy and on agar plates. These experiments showed that only selected cells were isolated, and close to 100% of the isolated stationary-phase cells formed colonies on agar plates, indicating a high recovery. A lower recovery was obtained with exponential-phase cells, possibly because of a higher sensitivity to laser irradiation. Applications for this method may include the isolation of mutants with altered morphology and the isolation of subpopulations of yeast cultures, for their separate investigation or for the initiation of pure cultures.     

Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis

This study examines the diagnostic utility of the polymerase chain reaction (PCR) in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected of extrapulmonary tuberculosis. The results of PCR in 226 samples from 11 different sites were compared with the results of microscopy and culture. Positive culture results were predicted in 86% of samples by PCR but in only 31% by microscopy. Specificity of PCR was 92%. In cases with culture-proven tuberculosis, PCR identified all 11 microscopy positive cases and 19 of 24 (79%) of the microscopy-negative cases. In four patients, PCR excluded the diagnosis of tuberculosis in microscopy-positive samples, which were later shown to contain mycobacteria other than Mycobacterium tuberculosis or laboratory contaminants. In 20 patients (microscopy, PCR and culture negative) a trial of antituberculous drugs was given, but patients showed no improvement and treatment was stopped. In 17 patients, all culture negative (in nine PCR was positive, three of whom also had positive microscopy) the diagnosis was probable tuberculosis based on clinical findings and response to treatment. This polymerase chain reaction has a much higher sensitivity than microscopy and can facilitate therapeutic decisions for those with suspected extrapulmonary tuberculosis.     

Analysis of information exchange activities to actualize and validate situation awareness during shift changeovers in nuclear power plants

Shift work situations occur in almost all safety‐critical organizations, and the investigations of some catastrophes like Chernobyl, Exxon Valdez, and the Gol/Legacy mid‐air collision indicated that shift work information exchange played an important role during the evolution of the situation before the accidents. Inadequate communications during shift changeovers challenged operators' work in the moments that preceded these accidents, because they got inadequate information about the current situation. Our research focuses on the information exchange activities (verbal, written, and nonverbal) of nuclear power plant control operators during shift changeovers. Our aim is to investigate how verbal exchanges and other representations enable operator crews to share information regarding the events that occurred in the previous shift to achieve adequate situation awareness. Our findings indicated the importance and richness of the information exchange during the shift changeover process to update and validate individual and collective situation awareness, showing that information adequately shared enables the ad hoc configurations of regulation loops and a safer use of simplified strategies that can be understood and be validated by other operators, reducing the occurrence of cognitive overloads and contributing to the construction of a common cognitive ground that enhances system resilience. © 2010 Wiley Periodicals, Inc.     

Constructive model-based analysis for safety assessment

The aerospace industry still uses fault trees to perform reliability analysis. This is because fault-tree modeling and analysis (FTA) seems easier to practical engineers when compared with Markov models, even though FTA provides a weaker form of analysis. In this paper, we propose an automatic strategy for generating Markov-based models and corresponding analysis formulations, according to ARP 4761, directly from Simulink diagrams annotated with failure information. The generated Markov-based models are expressed in the formal language PRISM, and the analysis is carried out by the PRISM model checker. The strategy is compositional and based on a comprehensive set of translation rules from Simulink to PRISM. We briefly address soundness and completeness of the rules and, to illustrate the application of the strategy, we apply it to a classical avionics case study: an actuator control system.     

Peptides to Tackle Leishmaniasis: Current Status and Future Directions

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources—amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others—or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.     

Global insight into microwave stoneware firing: Macro and microstructural changes

Industrial competition and environmental concerns lead to the exploration of alternative and energy-efficient technologies for ceramic materials processing. The main objective of this work was to present microwave heating as a viable option for stoneware processing. Stoneware functional properties are presented and discussed, with emphasis on impact strength, water absorption, porosity, and color. Microstructure analyses show that microwave- and gas-fired samples have higher densifications than electrically fired samples. A relevant finding for processing conditions is that microwave firing requires temperatures approximately 100°C lower than those required by conventional firing. Microwave-fired samples’ rupture energies are approximately twice (0.57 ± 0.06 (J)) those of the reference samples (0.26 ± 0.03 (J)), and their water absorptions are approximately one-half (1.5% at 1170°C and 0.8% at 1190°C) of those of the reference samples (2.0%), whereas the water absorption of electrically fired samples at 1180°C has been estimated to be 7.5%. Color analysis also evidences a shift to lower microwave firing temperatures, what is attributed to the enhanced transformations promoted by microwave heating when comparing with the transformations promoted by conventional (gas or electric) heating.